BACKGROUND Genetic analysis in model organisms such as yeast, C. elegans and fruit flies have resulted in many fundamental discoveries in basic biology. The lack of genetic tools in mammalian system has significantly hampered genetics studies in mammalian cells. The advent of RNAi technology have now made it possible to conduct such analysis. PURPOSE We aim to develop new mammalian vector systems to express shRNAs and cDNAs efficiently. This will enable us to introduce multiple, defined genetic changes into cells to create the desired genotype. SIGNIFICANT MATERIALS AND METHODS Expression vectors for shRNAs and cDNAs. FY2011 ACCOMPLISHMENT We have established a design for the vector and validated shRNAs against tumor suppressors.